RELATIONSHIPS BETWEEN IN-VITRO AND IN-VIVO BIOTRANSFORMATION OF DRUGSIN HUMANS AND ANIMALS - PHARMACOTOXICOLOGICAL CONSEQUENCES

Given the crucial role played by hepatocytes in the detoxification/tox ification processes of drugs, these cells have been increasingly used during the last decade in various pharmaco-toxicological areas. The ma jority of these studies have, however, dealt with animal cells, althou gh examples of failures in the extrapolation of the data to man are fr equent. This drawback, together with the ethical considerations in per forming in vivo experiments, makes the application of the human hepato cyte model critical in the preclinical evaluation of new compounds. Ho wever, before making extensive use of these promising tools for prospe ctive pharmaceutical research, one must ensure that they can generate data that correlate well with those obtained in vivo. This is only pos sible through extensive studies on drugs showing a variety of phase I and phase II metabolic pathways in hepatocytes from different species, including man, and comparison with in vivo data. Providing this valid ation step is undertaken, the use of such systems in drug research and development may greatly enhance the rational design of safe and effec tive drugs, allowing savings in time, cost and test materials as well as minimizing the use of animals.